The objectives of the proposed research are to study 1) the pathophysiologic and biochemical aberrations in the hyperuricemic and normouricemic gouty offspring as another approach to explore the nature of the metabolic defect in gout; 2) the coincidence of gout and diseases caused by or associated with atherosclerosis; 3) the role of kidneys in hyperuricemia; 4) the renal pathology in gout; 5) the metabolic rate of drugs and interactions; and 6) organic acid excretion and its relation to uric acid transport. Long term treatment of gout to be continued. Included in the study of the gouty offspring will be the incidence of hyperuricemia and hyperuricosuria, urinary NH4 excretion, plasma and urinary amino acid excretion pattern, amino acid loading, and in selected cases the rate of incorporation of uric acid N15 from labeled glycine. Coincidence of gout and diseases caused by or associated with atherosclerosis will be studied retrospectively and prospectively, and also correlation between hyperuricemia and hyperlipidemia among the asymptomatic hyperuricemics. With regard to the role of the kidneys in hyperuricemia, serial renal functions in gout and asymptomatic gouty offspring will be done. Kidney pathology from biopsy and autopsy material will be studied. Drug interaction between probenecid and pyrazinoic acid will be observed in man and dogs. Methods are being developed for quantitative estimation of the drugs and their metabolites on gas chromatography. Organic acid excretion and its competetion with uric acid transport is to be done in dogs. In man the organic acid excretion pattern will be studied in relation to the formation of renal calculi. A more accurate method for separation and quantitative determination of organic acid analysis is being developed.